Enhanced in vivo therapeutic efficacy of plitidepsin-loaded nanocapsules decorated with a new poly-aminoacid-PEG derivative.

Abstract

The focus of this study is to disclose a new delivery carrier intended to improve the pharmacokinetic characteristics of the anticancer drug plitidepsin and to favor its accumulation within the tumor. These nanocarriers named as nanocapsules, consist of an oily core surrounded by a highly PEGylated polyglutamic acid (PGA-PEG) shell loaded with plitidepsin. They showed a size of around 190 nm, a zeta potential of -24 mV and were able to encapsulate a high percentage (85%) of plitidepsin. In vivo studies, following intravenous injection in healthy mice, indicated that the encapsulation of the drug within PGA-PEG nanocapsules led to an important increase in its area under the curve (AUC) which is related to the important decrease of the clearance, as compared to the values observed for the drug dissolved in a Cremophor(®) EL solution. This improvement of the pharmacokinetic profile of the encapsulated plitidepsin was accompanied by a high increase (2.5-fold) of the maximum tolerated dose (MTD) in comparison to that of plitidepsin Cremophor(®) EL solution. The efficacy study performed in a xenograft tumor mice model evidenced the capacity of PGA-PEG nanocapsules to significantly reduce tumor growth. These promising results highlight the potential of PGA-PEG nanocapsules as an effective drug delivery system for cancer therapy.

• Authors: Giovanna Lollo, Pablo Hervella, Pilar Calvo, Pablo Avilés, Maria Jose Guillén, Marcos Garcia-Fuentes, Maria José Alonso, Dolores Torres
• Journal: International journal of pharmaceutics (Int J Pharm) Vol. 483 Issue 1-2 Pg. 212-9 (Apr 10 2015) ISSN: 1873-3476 [Electronic] Netherlands
• PMID: 25681727 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015. Published by Elsevier B.V.

Chemical References

• Antineoplastic Agents
• Depsipeptides
• Drug Carriers
• Nanocapsules
• Peptides, Cyclic
• Polyglutamic Acid
• Polyethylene Glycols
• plitidepsin

Topics

• Animals
• Antineoplastic Agents (administration & dosage, chemistry, pharmacology)
• Cell Proliferation (drug effects)
• Depsipeptides (administration & dosage, chemistry, pharmacology)
• Drug Carriers (administration & dosage, chemistry)
• Drug Delivery Systems
• Female
• Humans
• Injections, Intravenous
• Male
• Maximum Tolerated Dose
• Mice
• Mice, Nude
• Nanocapsules (administration & dosage, chemistry)
• Neoplasms, Experimental (drug therapy, pathology)
• Particle Size
• Peptides, Cyclic
• Polyethylene Glycols (administration & dosage, chemistry)
• Polyglutamic Acid (administration & dosage, chemistry)
• Surface Properties
• Xenograft Model Antitumor Assays